Neural microexons are very short exons that are expressed only in neurons, where they modify multiple proteins, including many that are essential for axon pathfinding. The goal of this project is to study their roles in vivo, using zebrafish as a model system.
Microexons are extremely short (3-27 nt) conserved exons found in the transcripts of specific genes involved in synaptogenesis and axon guidance. Deregulation of microexons is found in patients with autism, suggesting that their misregulation during brain development could result in neuronal wiring defects that lead to impairments in social behavior. The goal of this project is to test whether misregulation of selected axon pathfinding-specific microexons during brain development result in impairments of synaptogenesis or/and axon guidance that can lead to defects in social behavior.
Publication 1: Torres-Méndez, A., Bonnal, S., Marquez, Y., Roth, J., Iglesias, M., Permanyer, J., Almudí, I., O’Hanlon, D., Guitart, T., Soller, M., Gingras, A.-C., Gebauer, F., Rentzsch, F., Blencowe, B.J.B., Valcárcel, J., Irimia, M. (2019). A novel protein domain in an ancestral splicing factor drove the evolution of neural microexons. Nature Ecol Evol, 3:691-701.
Publication 2: Fernandez, J.P., Moreno-Mateos, M.A., Gohr, A., Miao, L., Chan, S.H., Irimia, M., Giraldez, A.J. (2018). RES complex is associated with intron definition and required for zebrafish early embryogenesis. PLoS Genet, 14:e1007473.
Publication 3: Burguera, D., Marquez, Y., Racioppi, C., Permanyer, J., Torres-Mendez, T., Esposito, R., Albuixech, B., Fanlo, L., D'Agostino, Y., Gohr, A., Navas-Perez, E., Riesgo, A., Cuomo, C., Benvenuto, G., Christiaen, L.A., Martí, E., D'Aniello, S., Spagnuolo, A., Ristoratore, F., Arnone, M.I., Garcia-Fernàndez, J., Irimia, M. (2017). Evolutionary recruitment of flexible Esrp-dependent splicing programs into diverse embryonic morphogenetic processes. Nat Commun, 8:1799.